The proposed study will examine in a scientific, controlled way the role of essential fatty acids (EFA) in the treatment of dry-eye disease (DED). Moderate to severe DED is an inflammatory disease, characterized by complaints of eye irritation, eye pain, foreign-body sensation, chronic red eyes, photophobia, fluctuation in vision, and/or loss of vision. DED is a widespread, growing problem with serious consequences. DED is the most common complaint to present in the ophthalmologist's office, with 10-20% of adults in the United States suffering from it. It appears to be more common in women than in men, particularly postmenopausal women. At present, moderate to severe DED is inadequately treated. EFA are polyunsaturated fatty acids which are essential in the human diet since they cannot be synthesized by the body. EFA have been shown in laboratory studies, animal models and some human clinical trials to ameliorate inflammatory reactions and they are widely available over the counter (OTC), purporting to combat or prevent diseases associated with inflammation, including DED, despite the fact that there have been no large, well-controlled and planned, randomized double-blind clinical trials to test the efficacy and safety of EFA for treatment of DED. The proposed study will address this gap in information. The specific aims of this Planning Grant are to resolve key issues in order to develop a detailed Manual of Operations, to document the ability to recruit suitable subjects, and to perform a small feasibility study to refine procedures and finalize the Manual of Operations for a multi-centered, randomized, placebo-controlled study of EFAs in moderate to severe DED. This is in line with NIH goals of increasing knowledge of ocular surface disease and inflammation, and of addressing human diseases more common in women, and will expand the evidence available on supplement-use to prevent and treat chronic disease.